ic11 schizophrenia Flashcards
Definition of psychosis
Acute episode of disorganised thoughts and speech, hearing things in the absence of stimuli
Definition of Schizophrenia
Onset of Schizophrenia
6 months of psychosis
onset: late teenage to adulthood
Causes of Schizophrenia (7 points)
Epilepsy
Tumours
CNS infection eg. Meningitidis
Endocrine eg. Hyperthyroidism
Substance abuse eg. alcohol, meth, benzodiazepine withdrawal
Parkinson’s disease medication
Dopamine agonists eg. Levodopa→ induce psychosis
Dementia
What is the diagnosis of Schizophrenia?
2 of the following, for at least 1 month
(1-4 are +ve symptoms, 5 is -ve)
1) Delusions
Bizarre belief that is fixated, despite evidence of the contrary
2) Hallucinations
Hearing imaginary voices, patient has no control over it
Seeing things eg. shadows
Smelling things
Taste
Touch
3) Disorganised speech
Manifestation of disorganised thoughts
4) Catatonic behavior (either react very little or too disruptive)
5) Negative symptoms
Affective flattening: dont smile, express emotions
Avolition: lack motivation
Cause social or occupational dysfunction
At least 6 months (including prodromal or residual symptoms)
Not due to medical disorder (eg. hyperthyroidism), substance use
Non pharm for Schizophrenia (3 points)
Cognitive Behavioural Therapy (CBT)
Used in conjunction with medications and family intervention
Electroconvulsive Therapy (ECT)
Reserved for treatment resistant Schizophrenia
Psychosocial rehab (integrate back into society)
What is the difference between Benzodiazepines and Antipsychotics?
Both used to calm patient down
BZD is solely to calm patient down, does not directly help with Schizophrenia. Will put patient to sleep or cause paradoxical excitement in young children and elderly
Antipsychotics can calm patient down without putting patient to sleep and without causing paradoxical excitement
Why do antipsychotics have sustained effect for a few weeks even after stopping
Antipsychotics are fat soluble, enter adipose tissue and act as depot to slowly release into blood
But relapse will still occur if withdrawn abruptly, after a few weeks
What is another indication of antipsychotics
Major Depressive Disorder
Aripiprazole
Brexpiprazole
Quetiapine XR
ic13 Bipolar disorder
Off label: Insomnia (low doses of Quetiapine)
when are IM injections indicated?
when patients are not adherent (either agitated or just not compliant) or dont prefer oral antipsychotic
Agitation -> typically administered smaller doses eg. Haloperidol 2.5mg
VS
Long acting antipsychotics for maintenance therapy eg. Haloperidol 25 - 50mg + formulated for prolonged release eg. decanoate
which LAI requires most frequent administration? what is the frequency?
Risperidone Consta requires every 2 weeks (and oral supplementation for first 3 weeks), the rest of LAI are once monthly
What pathway helps with Schizophrenia?
What pathway causes Schizophrenia side effects? (3 points)
Efficacy
Mesolimbic pathway (therapeutic effect)
Involved in (+) symptoms eg. emotion, cognition and attention
D2 receptor antagonism → target (+) symptoms
5HT2A antagonism → target (-) symptoms
Side effects
1) Nigrostriatal pathway
D1 and D2 antagonism, but D2 blockade causes less EPSE than D1
Involved in voluntary movement, hence D1D2 blockade will cause involuntary movement eg. acute dystonia, tardive dyskinesia, akathisia
2) Tuberoinfundibular pathway
Regulates prolactin secretion
Side effects caused by D2, D3 receptor antagonism by Amisulpride
3) Mesocortical Tract
Dopamine blockade will result or worsen existing (-) symptoms
Antagonism / agonism of which receptors will result in therapeutic effects?
Antagonise D2 and Serotonin 2A, agonise Serotonin 1A
D2 will improve (+) symptoms
HT2A will improve (-) symptoms
5HT1A will reduce anxiety
Antagonising receptors will result in adverse effects?
D2, Serotonin 2C, HAM (H1, alpha adrenergic, muscarinic)
Which receptor, when antagonised, will result in both therapeutic and adverse effects
D2
General traits of oral antipsychotics and exceptions
Short Tmax (1-3hrs)
Fast absorption, Fast onset
Long half life
Hence can combine multiple doses into single dose
Good for sedating antipsychotics eg. FGA, Olanzapine
Single dose can be taken in early evening if night dose causes patient to be tired the next morning
Exception: Quetiapine, Clozapine (QC before combining doses), as may cause seizures, hypotension
Similarity and difference between FGA and SGA in terms of improving symptoms of Schizophrenia
FGA and SGA can reduce (+) symptoms due to dopamine blockade
SGA can also reduce (-) symptoms due to 5HT2A serotonin antagonism
Side effects of FGA and SGA
FGA: more EPSE and prolactin secretion
“-pines” (SGA): more weight gain, blood sugar, cholesterol
Between Olanzapine (SGA) and Haloperidol (FGA), which is preferred? Why?
Olanzapine is preferred, due to weaker D2 antagonism, and hence lesser EPSE than Haloperidol
Which is the most commonly used antipsychotic?
Risperidone (due to high potency)
What is the treatment algorithm for Schizophrenia?
1) Use one FGA or SGA (except Clozapine)
2) Use another FGA or SGA (except Clozapine)
3) Clozapine (3rd line)
Why is Clozapine 3rd line?
Most effective antipsychotic!
1) Short half life
2) Anticholinergic
3) Risk of agranulocytosis (low neutrophils), cause opportunistic infections
Need to monitor FBC every week for 18 weeks
How long should patient take the medication before treatment is ineffective
Patient need to be 80% compliant for 2-6 weeks at optimal therapeutic dose before considered ineffective
What patient is contraindicated to take antipsychotics?
patients with QTc prolongation
In acute agitation, what can be offered if patient is cooperative?
What if patient is not cooperative
Cooperative, can give oral
Oral Lorazepam 1-2mg
Oral Risperidone 1-2mg
Uncooperative, consider fast acting IM injection
1) IM Lorazepam
2) IM Olanzapine (immediate release) (SGA)
Better than Haloperidol
Lesser D2 antagonism → EPSE (hand tremors, muscle stiffness)
3) IM Haloperidol (FGA)
If patient wakes up with muscle stiffness with Haloperidol, give IM Benztropine (anticholinergic)
4) IM Promethazine
Treatment for Catanonia?
PO or IM Lorazepam
ECT
Side effects of antipsychotics (6 points)
1) EPSE
2) Hyperprolactinemia
3) Metabolic
4) Cardiovascular
5) Neuroleptic malignant syndrome
6) Agranulocytosis
What is the cause of EPSE?
Which drug most commonly associated with EPSE?
Too much D2 antagonism at the nigrostriatal pathway
Haloperidol (FGA)
What are some ways to treat EPSE?
benztropine (an anticholinergic)
Reduce antipsychotic dose
Switch to SGA from Haloperidol (FGA)
4 types of EPSE and treatment
1) Dystonia
painful muscle contraction in the neck
Treatment: benztropine
2) Pseudo-parkinsonism
tremors, rigidity
Treatment: benztropine
3) Akathisia
Restlessness
Treatment: use Clonazepam or Propranolol
4) Tardive Dyskinesia
Involuntary movement of jaw, tongue
More common with FGA
Worsened with anticholinergics
Treatment: stop anticholinergics, treat with Valbenazine or Clonazepam
When can Benztropine be used / cannot be used?
Can: Dystonia, Pseudo-parkinsonism
Cannot: Tardive dyskinesia (anticholinergic will worsen it), Akathisia (anticholinergics ineffective)
What EPSE can Clonazepam be used to treat?
Akathisia and Tardive Dyskinesia
Treatment of Hyperprolactinemia
Switch to Aripiprazole
What are metabolic side effects, associated with which antipsychotic?
Treatment
Weight gain, increase blood sugar, increase cholesterol
Associated with “-pines”
Treatment: lifestyle modification / diet, Metformin, Use lower risk agent eg. Aripiprazole
Cardiovascular side effect examples
Orthostatic hypotension
QTc prolongation
patients with QTc prolongation contraindicated with Antipsychotics
Neuroleptic Malignant Syndrome symptoms
3 ways to get NMS
Lead pipe rigidity, muscle stiffness, fever, very high CK
Succinylcholine
Start potent IM antipsychotic
Suddenly stop Levodopa (as good as taking dopamine antagonist)
Treatment for NMS (3 points)
IV Dantrolene
Oral Dopamine agonist (eg. Amantadine, Bromocriptine)
Switch to SGA
Which drug associated with agranulocytosis?
Clozapine, Carbamazepine ic13)
need to monitor FBC every week for first 18 weeks
Monitoring for antipsychotics (6 points)
BMI
Fasting blood sugar
Lipid panel
Blood pressure
EPSE exam
WBC, ANC (for Clozapine)
Weekly for first 18 weeks
What antipsychotic should be used for elderly?
Avoid a1 blockade (orthostatic hypotension) and anticholinergic drugs (constipation, urinary retention, delirium), avoid long T1/2 drugs
Anticholinergic agents: FGA, Clozapine (SGA)
Use Quetiapine → short half life, is a SGA
Clozapine is a substrate of?
1A2
Which drugs should not be used with Clozapine?
Fluvoxamine (SSRI), is a 1A2 inhibitor
Carbamazepine, as itself can cause agranulocytosis also
How do dopamine agonists interact with Antipsychotics
Cancel out effect of Antipsychotics
Dopamine agonists eg. Levodopa, Bromocriptine, Amantadine
but can be used for NMS
Examples of 1A2 inducers (3 points)
Rifampicin (TB drug)
Ph Antiepileptics (Phenobarbital, Phenytoin)
Cigarette smoking
Examples of 1A2 inhibitors
Fluvoxamine
Quinolones
Macrolides
Time taken to see effects
1st week: agitation
2-4 weeks: paranoia, hallucinations
6-12 weeks: delusions, negative symptoms
5 things about Clozapine
1) Agranulocytosis
2) Anticholinergic
3) Short half life
4) Most effective in suicidal patients
5) 1A2 substrate
